ABSTRACT The goal of our proposal is to define the impact of premature aging in HIV seropositive subjects on the human eye. Antiretroviral therapy has dramatically improved the life expectancy of HIV+ subjects. Research indicates that HIV+ subjects experience age-related changes 10-15 years earlier than age-matched HIV- peers. The human retina offers a unique window into a section of the central nervous system (CNS). Currently, there is no biomarker for monitoring the effect of aging on the CNS. The secondary goal is the development of a surrogate biomarker in the eye for CNS damage. In this proposal we will use adaptive optical (AO) imaging to document cone photoreceptor density and retinal vascular morphometry. Our preliminary data suggests that HIV+ subjects have lower cone photoreceptor density. Other evidence indicates that changes to the microvasculature may be age-related. We will additionally acquire non-invasive vascular parameter using OCT angiography and metabolic data through lifetime fluorescence measurement in the eye (FLIO). We will use Carotid intima-media thickness as a cardiovascular surrogate biomarker. In addition, we will have access to other putative measures of biological aging (telomere length, mitochondrial common deletion, end-products of oxidative stress and DNA methylation) through the collaboration with the HNRC. By combining AO imaging, OCT angiography, and FLIO with our established structural data (SD-OCT, etc.) and putative measures of aging we can study the impact of premature aging on the eye. The data will be correlated with neurobehavioral, immunological and medical data collected by our collaborators at the HNRC. We plan to develop clinical reliable evaluation tools for risk assessment of premature aging. We will determine the prognostic capabilities of these evaluation tools with the help of biostatistical modeling.